Sordarin is an antifungal antibiotic isolated from the mould Sordaria araneosa (see GB 1,162,027 and Helvetica Chimica Acta, 1971, 51:119-20). Other compounds having the sordarin skeleton have also been reported as antifungal agents. Japanese Kokai J62040292 discloses the compound zofimarin isolated from Zofiela marina sp.; Japanese Kokai J06157582 discloses the compound BE-31405 isolated from Penicillium sp.; and SCH57404 is reported in J. Antibiotics, 1995, 48:1171-1772. Semi-synthetic sordarin derivatives are reported in PCT Applications WO96/14326 and WO96/14327.
Sordaricin, the aglycon, may be obtained from sordarin by acid hydroylsis (Hauser and Sigg, Helvetica Chimica Acta, 1971, 51:119-20); similarly sordaricin methyl ester is obtained from sordarin methyl ester. The total synthesis of sordaricin methyl ester is reported in Kato et al., J. Chem. Soc., Chem. Communi., 1993, 1002-1004, which also discloses O-methoxymethyl sordaricin methyl ester. The diacetate of 4-desformyl-4-hydroxymethyl sordaricin is disclosed in Mander and Robinson, J. Org. Chem., 1991, 56(11):3395-3601. Neither sordaricin nor the reported derivatives thereof has been shown to have biological activity. Cyano derivatives of the formyl group have not been previously described.